Association of sodium channel γ-subunit promoter variant with blood pressure
Association of sodium channel γ-subunit promoter variant with blood pressure
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DOI：
10.1161/01.hyp.38.1.86
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发表时间：
2001-07-01
期刊：
影响因子：
8.3
通讯作者：
Ogata, J
中科院分区：
文献类型：
--
作者：
Iwai, N;Baba, S;Ogata, J
SCNNIG基因位于人类染色体16p12上，编码对阿米洛利敏感的上皮性钠通道的伽马亚基，SCNNIG基因的突变可导致利德尔综合征或假性I型醛固酮减少症。我们鉴定了SCNNIG启动子区域的序列变异，并在代表日本普通人群的大队列(n=4075)中检测了该多态性与血压的相关性。我们在SCNNIG基因启动子区域发现了T(-1290)C、T(-501)G、G(173)A和G(-104)T多态，并证实了外显子3存在T387C和T474C多态，外显子13存在C1947G多态。由于T(-1290)C、T(-501)G、G(-104)T和T474C等位基因处于紧密连锁不平衡状态，我们选择了T474C和G(-173)A多态进行关联研究。SCNNIG基因G(-173)A多态对收缩压(P=0.0050)和脉压(P=0.0050)有显著影响。AA基因与收缩压下降I-I mm-Hg和脉压下降8 Nim-Hg相关，并与低血压发生率高相关(P=0.0195)。用MDCK细胞和人肾上皮细胞进行瞬时转染实验表明，G(-173)等位基因的启动子活性高于A(-173)等位基因。虽然A(-173)等位基因的影响是隐性的，尽管在我们的研究人群中只有0.7%的人发现了AA基因型，但我们观察到人类SCNNIG的这种变异对血压有显著影响。
The SCNNIG gene, located on human chromosome 16p12, encodes the gamma subunit of the amiloride-sensitive epithelial sodium channel, and mutations in SCNNIG can result in Liddle's syndrome or pseudohypoaldosteronism type I. We identified sequence variations in the promoter region of SCNNIG and examined the association between this polymorphism and blood pressure in a large cohort (n=4075) representing the general population in Japan. We found T(-1290)C, T(-501)G, G(-173)A, and G(-104)T polymorphisms in the promoter region of SCNNIG and confirmed the existence of T387C and T474C polymorphisms in exon 3 and the C1947G polymorphism in exon 13. Because the genotypes of the T(-1290)C, T(-501)G, G(-104)T, and T474C polymorphisms were in tight linkage disequilibrium, we selected the T474C and G(-173)A polymorphisms for an association study. The G(-173)A polymorphism of SCNNIG had a significant effect on systolic pressure (P=0.0050) and Pulse pressure (P=0.0050). The AA genotype was associated with an I I mm Hg drop in systolic pressure and an 8 nim Hg drop in pulse pressure and with a higher prevalence of hypotension (P=0.0195). A transient transfection assay using MDCK cells and human renal epithelial cells indicated that the promoter activity of the G(-173) allele was higher than that of the A(-173) allele. Although the effects of the A(-173) allele were recessive and although the AA genotype was found in just 0.7% of our study population, we observed that this variation of human SCNNIG had significant effects on blood pressure.